is methiopropamine a releaser or re-uptake inhibitor?

[T9358]

After some research I have found some conflicting data basically indicating that thiopropamine ( unmethylated) is a releaser were as MPA is a re-uptake inhibitor with a preference for NE over DA. It does not make sense to me as methylation of a compound in my knowledge should not alter its pharmacological action that much.

anybody have any info or clarification on this and the potency of MPA? thank you ahead of time

 

[Molecular_Man]

After some research I have found some conflicting data basically indicating that thiopropamine ( unmethylated) is a releaser were as MPA is a re-uptake inhibitor with a preference for NE over DA. It does not make sense to me as methylation of a compound in my knowledge should not alter its pharmacological action that much.

anybody have any info or clarification on this and the potency of MPA? thank you ahead of time

MPA seems that to behave more like amphetamine (releasing agent) than coke,methylphenidate (re-uptake inhibitor).
One study "Neurochemical profiles of some novel psychoactive substances" mentioned only about it's re-uptake inhibitor properties.

Does anyone have any studies on the mechanism of action?

 

[ungelesene_bettlek]

The very same question puzzles my mind right now (I know that the thread is five years old). According to Wikipedia it is a Noradrenaline and Dopamine reuptake inhibitor, but all releasing agents also act as reuptake inhibitors, so it seems likely to me that its action as a releasing agent has not been researched enough yet. Are there any new insights in this question?

 

[izo]

it is a releaser just like methamphetamine.

 

[Gaffy]

It acts as a releaser for dopa and ne, mimics dopa ne and sert to some extent, thus acting as a reuptake inhibitor as its binding is stronger to the ports for reuptake yet isn't taken up into the neuron. This causes electrochemical excitability in the neuron as it signals strong activity at its ports and as a result creates a strong release on its other side, causing a chain reaction etc.

 

[Gaffy]

MPA seems that to behave more like amphetamine (releasing agent) than coke,methylphenidate (re-uptake inhibitor).
One study "Neurochemical profiles of some novel psychoactive substances" mentioned only about it's re-uptake inhibitor properties.

Does anyone have any studies on the mechanism of action?

Coke, like most local anaesthetics, lowers the excitability treshold of neurons by acting on the electrochemical side of things (desensibilizes the cation channels causing a cascade in "inorganic" exchanges), wich causes most of the potential for a high. It's the reuptake inhibition potential of coke or for example blaezocaine that then causes a "natural" high with the naturally present neurotransmitters unlike ampas where the neurotransmitters are mimicked. See explanation above.

 

[ungelesene_bettlek]

it is a releaser just like methamphetamine.

Do you have sources for that? Preferred would be a scientific paper.

 

[izo]

it is indeed cited as a noradrenalin/dopamin reuptake inhibitor.

Neurochemical Profiles of some novel psychoactive substances

Fourteen substances from the class of drugs sometimes known as “legal highs” were screened against a battery of human receptors in binding assays, and their potencies as inhibitors of monoamine uptake determined in functional in vitro ...

www.ncbi.nlm.nih.gov

i thought bioisostere manipulation of the methamphetamine molecule might reveals just the same mechanism as an ne/dopamine releaser AND an reuptake inhibitor.

 

[Nagelfar]

After some research I have found some conflicting data basically indicating that thiopropamine ( unmethylated) is a releaser were as MPA is a re-uptake inhibitor with a preference for NE over DA. It does not make sense to me as methylation of a compound in my knowledge should not alter its pharmacological action that much.

anybody have any info or clarification on this and the potency of MPA? thank you ahead of time

I believe the substrate area to the external binding of a sole reuptake inhibitor is the difference of one methylene unit.